X-Ray and CT contrast agents

1. XRAY AND CT
CONTRAST AGENTS
BY DRNISHANT RAJ
POST GRADUATE RESIDENT
DMIMS, WARDHA

2. DEFINITION
Contrast media are substances used to highlight areas of the body in radiographic
contrast to their surrounding tissues.
Contrast media enhance the optical density of the area under investigation so that
the tissue absorption differentials are sufficient to produce adequate contrast with
adjacent structures, thus enabling imaging to take place.

3. TYPES OF CONTRAST
• Contrast media are divided into two main categories.
• The first is negative contrast media,
• Radiolucent
• Low atomic number, causing the part in which they
are placed to be more readily penetrated by X-rays
than the surrounding tissue; as they attenuate the X-
ray beam less effectively than body tissue.
• Appear darker on the X-ray image. Gases are
commonly used to produce negative contrast on
radiographic images.
• The second type is positive contrast media
• Radio-opaque
• High atomic number, causing the part in which they are
placed to be less readily penetrated by X-rays than the
surrounding tissue.
• Consequently, this contrast agent-filled area appears
denser than body tissue.
• Example: 1) Barium sulfate
USE: GI Studies.
• 2) Iodine compounds:
• USE: angiography, intravenous and retrograde
urography, hysterosalphingography ,sialography
myelography ,cholangiography.

4. IDEAL CONTRAST MEDIA
• High water solubility.
• Heat & chemical stability(shelf life) ideally- 3 to 5yrs.
• Biological inertness( non antigenic).
• Low viscosity.
• Low or iso-osmolar to plasma.
• Selective excretion, like excretion by kidney is favorable.
• Safety: LD50 (lethal dose) should be high.
• Reasonable cost.

5. CLASSIFICATION

6. BARIUM SULPHATE
• Atomic number:56
• Highly radiopaque
• Non absorbable.
• Non toxic.
• Insoluble in water/lipid.
• Inert to tissues.
• Can be used for double contrast studies.
• Route: Orally Or Rectally (aqueous
suspension with 0.3 to 1 g dry weight per
milliliter)
• Uses:
1. Barium swallow
2. Barium meal
3. Barium meal follow through
4. Enteroclysis
5. Barium enema

10. CONTRAINDICATION
• Integrity of gut wall compromised or GI Perforation.
• Previous allergic reactions to barium.
• Suspected fistula between oesophagus and lung.

11. WATER SOLUBLE IODINATED CONTRAST
MEDIA
• Majority of I.V contrast media used in CT contain Iodine,
• It is preferred because:
1. High contrast density due to high atomic number.(53)
2. Low toxicity
3. Allows firm binging to highly variable benzene ring.
• Radio-opacity depends on: Iodine concentration of the solution, so dependent on
number of iodine atoms in each molecule of the contrast medium.
• Iodine particle ratio: The ratio of number of iodine atoms per molecule to the number
of osmotically active particles per molecule of solute in solution.
• Not used in MRI

12. WATER SOLUBLE IODINATED CONTRAST
MEDIA
Routes of Administration:
1. Oral
2. Rectal
3. Intravenously
4. Intravertebral
5. Intrathecal (iohexol) & Intravesical

13. WATER SOLUBLE IODINATED CONTRAST
MEDIA
• Basic building block is benzene ring with three iodine molecules attached at
positions 2, 4, and 6.
• Side chains (at positions 3 and 5) are modified with hydroxyl groups or other
molecules that further define an agent’s properties.
• Exist as monomers (one benzene ring) or dimers (two benzene rings).
• Three defining physical characteristics of iodinated contrast agents: ionicity,
osmolality, and viscosity—play a distinct role in the tolerance and adverse
reaction profiles.

14. IONICITY: IONIC VS NON-IONIC
Ionic
• Dissolve into solution into anion and
cation
• Usually have high osmolality
• Associated with more Adverse
Effects
Non-Ionic
• Dissolve into water; but do not
dissociate
• Lower osmolality (fewer particles in a
solution compared to ionic)
• Lower incidence of AEs – hydrophilic,
reduced protein binding, low
tendency to cross cell membranes

15. OSMOLALITY
• In general, the higher the osmotic pressure the poorer the tolerance. Ionic
contrast media undergo this dissociation, whilst newer, non-ionic contrast media
do not.
• Osmolality is directly responsible for a number of clinically important effects
• Both the viscosity of a contrast medium and its osmolality are INVERSELY related
to tolerance but directly to degree of opacification.
• With increasing strength of contrast medium, the opacifying power of the solution
increases, but so, of course, do the osmolality and viscosity, while tolerance tends
to decline.

16. VISCOSITY
• The practical importance of viscosity of a contrast medium relates chiefly to the
force that is required to inject .
• Viscosity increases as concentration increases and tends to be higher for big
size molecules. (Dimers).
• High viscosity interferes with mixing of contrast media with plasma and body
fluids.

17. IODINATED CONTRAST MEDIA
IODINATED
CONTRAST
MEDIA
HIGH
OSMOLAR
IONIC
MONOMER
LOW
OSMOLAR
IONIC
DIMER
NON-IONIC
MONOMER
NON-IONIC
DIMER

18. IONIC MONOMER/CONVENTIONAL CONTRAST
MEDIA
• Salts with sodium or meglumine(N-methylglucamine) as the non-
radiopaque cation and a radiopaque tri-iodinated fully substituted
benzoic acid ring as the anion.
• Triiodinated at C2, C4 & C6 of benzene ring.
• Completely dissociates in water solution therefore provides 3 iodine
atoms for two ions, giving iodine : particle ratio of 3:2
• Hypertonic, 6-8 times higherosmolality (>1400mosm/kg) than human
plasma.
• Examples: Diatrizoic Acid: Urograffin, Trazograff etc
• Iothalamic acid(Conray, Triovideo)
• Replaced by non-ionic low osmolar contrast media

20. DISADVANTAGES OF HIGH OSMOLAR
CONTRAST MEDIA
• Osmolar concentration is very high i.e upto 8 times of the physiological level.
• Osmolar challenge to every cell, tissue and fluid in the body is responsible for
their adverse effects.

21. LOW OSMOLAR CONTRAST MEDIA
• Ionic Dimer
• Non-Ionic Monomer
• Non-Ionic Dimer

22. IONIC DIMER
• Ioxaglate (Hexabrix)
• Only compound, mixture of sodium and
meglumine salts .
• Two benzene rings (each with 3 iodine
atoms) are linked by a bridge to form a
large compound, carries only one
carboxyl group, so known as monoacid
dimers.
• Molecular weight is= 1269
• Osmolality : 560 osmol/kg H2O
• Iodine Particle ratio is 6:2

23. NON-IONIC MONOMER
• Carboxyl group (-COOH) at C-1 is replaced by non ionising
radical & CONH2
• Iodine:Particle ratio is 3:1
• Metrizamide(Amipaque) was the earliest non-ionic monomer and
proved as an excellent contrast media but was very expensive,
impossible to autoclave and unstable in solution.
• Osmolality is around 600 mosmols/kg
• Second Generation NIM are:
• Iohexol(omnipaque)
• Iopamidol(Iopamiro)
• Ioversol(optiray)
• Iopromide(Ultravist)

24. NON-IONIC DIMER
• Each molecule contains 2 non
ionising triiodinated benzene rings
linked together
• Iodine:Particle ratio is 6:1
• Molecular weight= 1550-1626
• Osmolality is around 300 mosmols/kg
• Eg: Iotrol, Iotrolan(Isovist)

25. ADDITIVES USED IN CONTRAST MEDIA
• Stabilizer: Ca or Na EDTA
• Buffers: Stabilizes pH during storage- Na Acid Phosphatases
• Preservatives.

26. PHYSIOLOGY OF WATER SOLUBLE IODINATED
CONTRAST MEDIA
• Concentration and Excretion mainly
via passive glomerular filtration.
• Net Tubular Excretion and protein
binding is negligible in the dose used.
• Liver and Intestine excrete 1% of
these compounds.
• Plasma life is 30-60 mins

27. IMPORTANT POINTS
• Contrast media used for myelography- non-ionic CM.
• CM used for cerebral angiography- only meglumine salt.
• Least osmolar- Ioxaglate (Hexabrix).
• Most hyperosmolar- Iohexol.
• Max nausea & vomiting- Ioxaglate (Hexabrix).
• Bronchospasm- Meglumine salts.
• Least viscosity- Omnipaque240
• Meticulous heparinization is required during angiography as incidence of
thromboembolic phenomenon is high when contrast is mixed with blood.

28. THANK YOU